Recent studies showed deposition of thrombotic material in intraoperative and early operative periods. We developed a canine model for these early periods. The model reproduced two essential characteristics of the clinical situation: (1) veins were not damaged directly during surgery and (2) veins were some distance from the surgical site. Healthy dogs anesthetized were subjected to hysterectomy, splenectomy, and intestinal anastomoses and compared with nonoperated controls. Clinical studies with low dose heparin have identified important differences in the response of patients to abdominal surgery and to hip replacement. Low dose heparin reduces the incidence of venous thrombosis dramatically after general surgery but had modest or no effects after hip replacement. Our preliminary studies showed gross tearing of the endothelial sheet around half the side branches following hip replacement. This did not occur after abdominal surgery. We propose that procedures involved in hip replacement cause release or generation of highly active substances (histamine, serotonin, bradykinin, other), a part of which finds its way into the circulation and affects all blood vessels before inactivation. Consequences of this are increased permeability and overt damage of endothelium caused by excessive vasodilation. To test this hypothesis we will: (1) monitor the blood pressure of control and hip replacement dogs for a period of 5-6 hours, starting before surgery and continuing for 4 hours after; (2) Monitor the diameter of vein(s) and side branches by ultrasound before, during and after surgery; (3) Inject 125I-albumin and Evan's blue dye to measure permeability of endothelium in operated and control dogs, and; (4) Remove blood by whole body perfusion (starting 4 hours after completion of surgery or after the same length of time under anesthesia controls), partially fix vessels in situ, remove the vessels and prepare for scanning and transmission electron microscopy and examine for the condition of endothelium and the adhesion of blood cells.